). In order to take full advantage of the clinical gene therapy opportunities offered by synthetic nonviral gene delivery systems, their efficacy needs to be improved, and one way to identify improved synthetic vectors is to screen a large number of candidates in a quantitative, efficacy indicating assay. A high throughput assay which enables 2000 transfection conditions to be quantitatively screened per week is available. From a compound library consisting of 144 pure cationic amphiphiles, 13 compounds were selected at random and 2 compounds were found with gene delivery potency exceeding that of the most potent commercially available cationic lipid reagents. Hence, this library may contain more compounds with equal or even greater potency. The grant will be used to synthesize 10 grams of the most active compound identified so far, and to screen the rest of the lipids in the library. The database from this quantitative survey will be used to develop structure activity relationships to guide the synthesis of more potent cationic lipid analogs and to identify more candidates for commercialization. PROPOSED COMMERCIAL APPLICATION: The cationic lipid formulations identified from this screening activity will be commercialized as tranfection reagents for scientists. Ultimately some of these formulation may become commercialized as human pharmaceutical gene therapy products.